1. Field of the Invention
This invention relates to an apparatus and method for monitoring the instantaneous concentration of singlet oxygen produced during photoradiation when a CW excitation source is used to excite a photodynamic sensitizer and also the means for processing the resultant data.
2. Background and Technical Summary
When certain non-toxic photodynamic sensitizers, such as hematoporphyrin derivative (HPD) and components thereof, are injected intravenously into the human body, they are selectively retained by cancerous tissue. Thus, two or three days after injection, significantly higher levels of the photodynamic sensitizer are retained in malignant tissue. The selective retention of hematoporphyrin derivative by cancerous tissue was first used clinically as a diagnostic tool. In the presence of ultraviolet or shortwave length visible light, such tissue will exhibit a bright red fluorescence while normal tissue appears light pink. A discussion of clinical investigations using this diagnostic technique can be found in an article entitled "Hematoporphyrin Diacetate: A Probe to Distinguish Malignant from Normal Tissue by Selective Fluorescence" by R. W. Henderson, G. S. Christie, P. S. Clezy and J. Lineham, Brit.J. Exp. Pathol., Vol. 61, pages 325-350 (1980). Another reference by D. R. Doiron and A. E. Profio entitled "Laser Fluorescence Bronchoscopy for Early Lung Cancer Localization" published in Lasers in Photomedicine and Photobiology (1980) teaches the use of a laser fluorescence bronchoscope to detect and localize small lung tumors by observing this red fluorescence.
An additional clinical application has recently been found in the treatment and destruction of malignant tissue, this treatment being referred to variously as photochemotherapy, photodynamic therapy or photoradiation therapy all of which are to be considered equivalent. The overall process by which biological damage occurs as the result of optical excitation of the photodynamic sensitizer in the presence of oxygen, is generally referred to as "photodynamic action". As indicated above, photochemotherapy involves the intravenous injection of a sensitizer derived from hematoporphyrin into the patient. After the passage of several days, usually three, the HPD sensitizer (or components thereof) is retained in significant amounts by cancerous tissue, however being eliminated by healthy tissue. The tumor is then exposed to a therapeutic light and this light energy causes the photodynamic sensitizer to be excited to an energetic metastable triplet state. Through a direct intermolecular process, the sensitizer transfers this energy to oxygen molecules present in the tissue and raises them from the ground triplet to the first excited electronic singlet state, .sup.1 O.sub.2 [symbolic designation of molecular oxygen in the .sup.1 .DELTA..sub.g electronic state]. The singlet oxygen, .sup.1 O.sub.2, attacks and functionally destroys the cell membranes ultimately inducing necrosis and destroying the cancerous tissue.
In an article by Thomas J. Dougherty et al entitled "Photoradiation Therapy for the Treatment of Malignant Tumors" published in Cancer Research, Vol. 38, pages 2628-2635 (1978), problems associated with prescribing the correct therapeutic light dosages are discussed. If the dosage is too weak, the tumor response will be partial or incomplete. If the irradiation time is too long or intensity too high, normal skin or tissue will experience necrosis. The aforementioned article points out the difficulty of determining the correct therapeutic dosage of light. This problem has been proven to be quite significant and currently is one of the major hurdles that must be overcome before photochemotherapy can be used to treat tumors in a systematic and reliable fashion.
Other clinical applications of photoradiation therapy are being investigated which also point out the urgent need to develop an apparatus and method for monitoring the instantaneous generation of singlet oxygen.